Treatment of dry eye restoring 15-lipoxygenase activity to ocular surface cells

Abstract

The present invention provides compositions comprising the 15-lipoxygenase-1 (15-LO-1) or 15-lipoxyngenase-2 (15-LO-2) gene such that 15-LO-1 or 15-LO-2 protein expression is replaced or replenished in the ocular surface epithelium of post-menopausal women suffering from dry eye. Thus, methods for treatment of dry eye in postmenopausal women are further provided.

1 . A method for treating dry eye, said method comprising: 
 a) obtaining a composition comprising SEQ ID NO:1 or SEQ ID NO:3; and    b) administering said composition to a patient suffering from dry eye under conditions such that SEQ ID NO:1 or SEQ ID NO:3 is expressed.    
     
     
         2 . The method of  claim 1 , wherein said composition comprises a vector comprising the sequence set forth in SEQ ID NO:1 or SEQ ID NO:3  
     
     
         3 . The method of  claim 1 , wherein said administering is by topical ocular drops or ointment.  
     
     
         4 . A composition for treatment of dry eye, said composition comprising a vector comprising the sequence set forth in SEQ ID NO:1 or SEQ ID NO:3 and a pharmaceutically acceptable excipient.  
     
     
         5 . A method of treating dry eye in a postmenopausal patient, said method comprising incorporating nucleic acid into an in situ ocular cell under conditions permissive for the uptake of said nucleic acid, said nucleic acid encoding a protein having the sequence set forth in SEQ ID NO:2, whereby said nucleic acid is expressed and said disease is treated.  
     
     
         6 . The method of  claim 6 , wherein said nucleic acid sequence comprises the sequence set forth in SEQ ID NO:1.  
     
     
         7 . The method of  claim 7 , wherein said cell is a conjunctival or corneal epithelial cell.  
     
     
         8 . The method of  claim 8 , wherein said cell is debrided prior to introducing said exogenous nucleic acid.  
     
     
         9 . The method of  claim 6 , wherein said nucleic acid is in a viral vector.  
     
     
         10 . The method of  claim 6 , wherein said nucleic acid is in a plasmid.  
     
     
         11 . The method of  claim 10 , wherein said nucleic acid is in a retrovirus.  
     
     
         12 . The method of  claim 10 , wherein said nucleic acid is in an adenovirus.  
     
     
         13 . The method of  claim 10 , wherein said nucleic acid is in an adeno-associated virus.  
     
     
         14 . A method of treating dry eye in a postmenopausal patient, said method comprising incorporating nucleic acid into an in situ ocular cell under conditions permissive for the uptake of said nucleic acid, said nucleic acid encoding a protein having the sequence set forth in SEQ ID NO:4, whereby said nucleic acid is expressed and said disease is treated.  
     
     
         15 . The method of  claim 15 , wherein said nucleic acid sequence comprises the sequence set forth in SEQ ID NO:3.  
     
     
         16 . The method of  claim 16 , wherein said cell is a conjunctival or corneal epithelial cell.  
     
     
         17 . The method of  claim 7 , wherein said cell is debrided prior to introducing said exogenous nucleic acid.  
     
     
         18 . The method of  claim 15 , wherein said nucleic acid is in a viral vector.  
     
     
         19 . The method of  claim 15 , wherein said nucleic acid is in a plasmid.  
     
     
         20 . The method of  claim 19 , wherein said nucleic acid is in a retrovirus.  
     
     
         21 . The method of  claim 19 , wherein said nucleic acid is in an adenovirus.  
     
     
         22 . The method of  claim 19 , wherein said nucleic acid is in an adeno-associated virus.